Many human brain disorders are caused by the phenomenon of glutamate excitotoxicity, including ischemia, Alzheimer's disease, Huntington's disease, and epilepsy. Using a rat model which shows an abnormal change in glutamate receptors in two brain regions (cerebellum and hippocampus), my research focuses on the effects that a dysfunctional receptor system has on the mammalian brain. Specifically, can a brain region be spared excitotoxic death using various drugs designed to block glutamatergic transmission? During the time frame of this proposal, my students and I will examine the neuroprotective abilities of various glutamate (NMDA and non-NMDA) antagonists. We will investigate the ability of these drugs to: 1. Increase survival of the mutant; 2. Reduce cell loss in a dose-response manner; and 3. Alter cellular glutamate receptor levels. The results of these studies will be useful in planning new neuroprotective strategies (drugs and dosage) for human victims of glutamate excitotoxicity. This research is designed to attract an increasing number of minority students interested in biomedical research.